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A simple model of immune and muscle cell crosstalk during muscle regeneration
Mathematical Biosciences ( IF 1.9 ) Pub Date : 2021-01-16 , DOI: 10.1016/j.mbs.2021.108543
Hristo V Kojouharov 1 , Benito M Chen-Charpentier 1 , Francisco J Solis 2 , Claudia Biguetti 3 , Marco Brotto 3
Affiliation  

Muscle injury during aging predisposes skeletal muscles to increased damage due to reduced regenerative capacity. Some of the common causes of muscle injury are strains, while other causes are more complex muscle myopathies and other illnesses, and even excessive exercise can lead to muscle damage. We develop a new mathematical model based on ordinary differential equations of muscle regeneration. It includes the interactions between the immune system, healthy and damaged myonuclei as well as satellite cells. Our new mathematical model expands beyond previous ones by accounting for 21 specific parameters, including those parameters that deal with the interactions between the damaged and dead myonuclei, the immune system, and the satellite cells. An important assumption of our model is the replacement of only damaged parts of the muscle fibers and the dead myonuclei. We conduce systematic sensitivity analysis to determine which parameters have larger effects on the model and therefore are more influential for the muscle regeneration process. We propose additional validation for these parameters. We further demonstrate that these simulations are species-, muscle-, and age-dependent. In addition, the knowledge of these parameters and their interactions, may suggest targeting or selecting these interactions for treatments that accelerate the muscle regeneration process.



中文翻译:

肌肉再生过程中免疫和肌肉细胞串扰的简单模型

衰老过程中的肌肉损伤会使骨骼肌因再生能力降低而增加损伤。肌肉损伤的一些常见原因是拉伤,而其他原因则是更复杂的肌肉肌病和其他疾病,甚至过度运动也会导致肌肉损伤。我们基于肌肉再生的常微分方程开发了一个新的数学模型。它包括免疫系统、健康和受损的肌核以及卫星细胞之间的相互作用。我们的新数学模型通过考虑 21 个特定参数,包括处理受损和死亡肌核、免疫系统和卫星细胞之间相互作用的参数,扩展了之前的数学模型。我们模型的一个重要假设是仅替换受损部分的肌肉纤维和死肌核。我们进行系统的敏感性分析,以确定哪些参数对模型的影响更大,因此对肌肉再生过程的影响更大。我们建议对这些参数进行额外验证。我们进一步证明这些模拟与物种、肌肉和年龄有关。此外,对这些参数及其相互作用的了解可能会建议针对或选择这些相互作用来加速肌肉再生过程的治疗。我们建议对这些参数进行额外验证。我们进一步证明这些模拟与物种、肌肉和年龄有关。此外,对这些参数及其相互作用的了解可能会建议针对或选择这些相互作用来加速肌肉再生过程的治疗。我们建议对这些参数进行额外验证。我们进一步证明这些模拟与物种、肌肉和年龄有关。此外,对这些参数及其相互作用的了解可能会建议针对或选择这些相互作用来加速肌肉再生过程的治疗。

更新日期:2021-02-05
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